Characterization of viral reservoirs among HIV-1 non-B vertically infected adolescents receiving antiretroviral therapy: A study protocol for an observational and comparative study in Cameroon, the “EDCTP AVIR Study” (Preprint)

BACKGROUND Antiretroviral therapy (ART) can bring HIV-1 in blood plasma to level undetectable by standard tests and allow a near-normal life expectancy for HIV-infected individuals. Unfortunately, ART is not curative and must be taken for life, as within a few weeks of treatment cessation, HIV viremia rebounds in most patients except for rare elite or post-treatment controllers of viremia. The primary source of this rebound is the highly stable reservoir of latent yet replication-competent HIV-1 proviruses integrated into the genomic DNA of resting memory CD4+ T cells. To achieve a cure for HIV, understanding the cell reservoir environment is of paramount importance. The size and nature of viral reservoir might vary per timing of therapy, therapeutic response, ART duration, and immune response. Mechanisms of reservoir maintenance generally depend on levels/type of immune recognition; in addition, dynamics of viral persistence are different between pediatric and adult populations. This difference could become more evident as these children grow toward adolescence, a stage during which suboptimal adherence is frequent, leading to viral rebound and archiving of resistant patterns. OBJECTIVE We plan to conduct a study with the aim to characterize HIV reservoirs and their variability per virological and immunological profiles of non-B HIV-1 vertically infected adolescents receiving antiretroviral therapy. METHODS This study will involve HIV-1 non-B infected adolescents aged 10-19 years vertically infected, have been on ART for at least 12 months, selected from an existing cohort in our research institution. Intravenous blood will be collected for immunological/virological profile including CD4/CD8 count, plasmatic viral load, immune activation/inflammatory markers, genotyping (protease and reverse transcriptase) and quantification of HIV-1 viral reservoirs. We will as well recruit an age matched group of HIV-negative adolescents as control for immunological profiling. RESULTS Our findings will help in advancing knowledge on HIV reservoirs, in terms of size and genetic variability in adolescents living with HIV (ADLHIV). CONCLUSIONS Evidence from this study will help in understanding the effects of ART timing and duration on the size of reservoirs among ADLHIV, a unique population from whom findings generated will largely contribute in designing functional cure strategies.